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Molecular subtypes of urothelial carcinoma are defined by specific gene regulatory systems

Overview of attention for article published in BMC Medical Genomics, May 2015
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3 tweeters

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46 Mendeley
Title
Molecular subtypes of urothelial carcinoma are defined by specific gene regulatory systems
Published in
BMC Medical Genomics, May 2015
DOI 10.1186/s12920-015-0101-5
Pubmed ID
Authors

Pontus Eriksson, Mattias Aine, Srinivas Veerla, Fredrik Liedberg, Gottfrid Sjödahl, Mattias Höglund

Abstract

Molecular stratification of bladder cancer has revealed gene signatures differentially expressed across tumor subtypes. While these signatures provide important insights into subtype biology, the transcriptional regulation that governs these signatures is not well characterized. In this study, we use publically available ChIP-Seq data on regulatory factor binding in order to link transcription factors to gene signatures defining molecular subtypes of urothelial carcinoma. We identify PPARG and STAT3, as well as ADIRF, a novel regulator of fatty acid metabolism, as putative mediators of the SCC-like phenotype. We link the PLK1-FOXM1 axis to the rapidly proliferating Genomically Unstable and SCC-like subtypes and show that differentiation programs involving PPARG/RXRA, FOXA1/GATA3 and HOXA/HOXB are differentially expressed in UC molecular subtypes. We show that gene signatures and regulatory systems defined in urothelial carcinoma operate in breast cancer in a subtype specific manner, suggesting similarities at the gene regulatory level of these two tumor types. At the gene regulatory level Urobasal, Genomically Unstable and SCC-like tumors represents three fundamentally different tumor types. Urobasal tumors maintain an apparent urothelial differentiation axis composed of PPARG/RXRA, FOXA1/GATA3 and anterior HOXA and HOXB genes. Genomically Unstable and SCC-like tumors differ from Urobasal tumors by a strong increase of proliferative activity through the PLK1-FOXM1 axis operating in both subtypes. However, whereas SCC-like tumors evade urothelial differentiation by a block in differentiation through strong downregulation of PPARG/RXRA, FOXA1/GATA3, our data indicates that Genomically Unstable tumors evade differentiation in a more dynamic manner.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 46 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Denmark 1 2%
Sweden 1 2%
Unknown 44 96%

Demographic breakdown

Readers by professional status Count As %
Researcher 17 37%
Student > Ph. D. Student 10 22%
Student > Master 5 11%
Student > Bachelor 4 9%
Student > Postgraduate 3 7%
Other 7 15%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 17 37%
Agricultural and Biological Sciences 14 30%
Medicine and Dentistry 9 20%
Unspecified 5 11%
Pharmacology, Toxicology and Pharmaceutical Science 1 2%
Other 0 0%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 January 2016.
All research outputs
#3,306,746
of 7,062,006 outputs
Outputs from BMC Medical Genomics
#227
of 397 outputs
Outputs of similar age
#104,953
of 213,052 outputs
Outputs of similar age from BMC Medical Genomics
#15
of 30 outputs
Altmetric has tracked 7,062,006 research outputs across all sources so far. This one has received more attention than most of these and is in the 50th percentile.
So far Altmetric has tracked 397 research outputs from this source. They receive a mean Attention Score of 4.4. This one is in the 38th percentile – i.e., 38% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 213,052 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 46th percentile – i.e., 46% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 30 others from the same source and published within six weeks on either side of this one. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.